lurkythere t1_ja8s5ye wrote
Yes! PCHDH19-related epilepsy only occurs in heterozygotes. Basically, neurons will express a particular type of cellular junction based on the version of PCDH19 expressed in that cell. If all neurons are mutant, it does not cause problems. But, if there are both variant and wild type neurons present, the mismatch leads to severe epilepsy. This is further complicated by the fact that PCDH19 is on the X chromosome, so males are typically hemizygous (only one copy of the gene) and therefore females are the only ones expected to be affected. This is a reversal of what we typically see in X linked disorders. Homozygous females are also not affected.
Things like Klinefelter syndrome (XXY male), mosaicism, and skewed X inactivation can add even more complexity. But again, it all comes down to whether there are more than one type of PCDH19 being expressed. The fact that males with Klinefelter can have PCDH19 related epilepsy demonstrates that this is not a sex limited disorder, but rather a heterozygote (or mosaic) limited disorder.
http://epilepsygenetics.net/the-epilepsiome/pcdh19-this-is-what-you-need-to-know/
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